Rapid IL-4 Production by Leishmania Homolog of Mammalian RACK1-Reactive CD4+ T Cells in Resistant Mice Treated Once with Anti-IL-12 or -IFN-γ Antibodies at the Onset of Infection with Leishmania major Instructs Th2 Cell Development, Resulting in Nonhealing Lesions

摘要

Rapid production of IL-4 by Leishmania homolog of mammalian RACK1 (LACK)-reactive CD4+ T cells expressing the Vβ4-Vα8 TCR chains has been shown to drive aberrant Th2 cell development and susceptibility to Leishmania major in BALB/c mice. In contrast, mice from resistant strains fail to express this early IL-4 response. However, administration of either anti-IL-12 or -IFN-γ at the initiation of infection allows the expression of this early IL-4 response in resistant mice. In this work we show that Leishmania homolog of mammalian RACK1-reactive CD4+ T cells also expressing the Vβ4-Vα8 TCR chains are the source of the early IL-4 response to L. major in resistant mice given anti-IL-12 or -IFN-γ Abs only at the onset of infection. Strikingly, these cells were found to be required for the reversal of the natural resistance of C57BL/6 mice following a single administration of anti-IL-12 or -IFN-γ Abs. Together these results suggest that a deficiency in mechanisms capable of down-regulating the early IL-4 response to L. major contributes to the exquisite susceptibility of BALB/c mice to L. major .